OBJECTIVE: The overlap between genetic susceptibility to celiac disease (CD) and to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may significantly modify the risk of CD in subjects with type 1 diabetes. This study aimed to investigate whether the susceptibility to CD in diabetic children is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by alleles of single nucleotide polymorphisms within the genes encoding CTLA4, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-2, IL-6, and IL-10. RESEARCH DESIGN AND METHODS: Genotypic data were compared between 130 case subjects (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and 245 control subjects (children with type 1 diabetes only, optimally two per case, matched for center, age at type 1 diabetes onset, and type 1 diabetes duration). The subjects were recruited from 10 major European pediatric diabetes centers performing regular screening for CD. The polymorphisms were determined using PCR with sequence-specific primers, and the risk was assessed by building a step-up conditional logistic regression model using variables that were significantly associated with CD in the univariate analysis. RESULTS: The best-fitted model showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds ratio 4.5 [95% CI 1.8-11], for homozygosity, and 2.0 [1.1-3.7], for a single dose) and also independently by TNF -308A (1.9 [1.1-3.2], for phenotypic positivity), whereas IL1-alpha -889T showed a weak negative association (0.6 [0.4-0.9]). CONCLUSIONS: The results indicate that the risk of CD in children with type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, the TNF -308A.
OBJECTIVE: The overlap between genetic susceptibility to celiac disease (CD) and to type 1 diabetes is incomplete; therefore, some genetic polymorphisms may significantly modify the risk of CD in subjects with type 1 diabetes. This study aimed to investigate whether the susceptibility to CD in diabeticchildren is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03 and by alleles of single nucleotide polymorphisms within the genes encoding CTLA4, transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1, IL-2, IL-6, and IL-10. RESEARCH DESIGN AND METHODS: Genotypic data were compared between 130 case subjects (children with type 1 diabetes and CD diagnosed using endomysium antibodies) and 245 control subjects (children with type 1 diabetes only, optimally two per case, matched for center, age at type 1 diabetes onset, and type 1 diabetes duration). The subjects were recruited from 10 major European pediatric diabetes centers performing regular screening for CD. The polymorphisms were determined using PCR with sequence-specific primers, and the risk was assessed by building a step-up conditional logistic regression model using variables that were significantly associated with CD in the univariate analysis. RESULTS: The best-fitted model showed that risk of CD is increased by presence of HLA-DQB1*02-DQA1*05 (odds ratio 4.5 [95% CI 1.8-11], for homozygosity, and 2.0 [1.1-3.7], for a single dose) and also independently by TNF -308A (1.9 [1.1-3.2], for phenotypic positivity), whereas IL1-alpha -889T showed a weak negative association (0.6 [0.4-0.9]). CONCLUSIONS: The results indicate that the risk of CD in children with type 1 diabetes is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, the TNF -308A.
Authors: Sjoerd F Bakker; Maarten E Tushuizen; Boudewina M E von Blomberg; Hetty J Bontkes; Chris J Mulder; Suat Simsek Journal: Diabetol Metab Syndr Date: 2016-07-29 Impact factor: 3.320
Authors: Miren Vicuña Arregui; Jose Manuel Zozaya Urmeneta; Helena León Brito; Juan Pablo Martínez De Esteban; Carlos Prieto Martínez; Lluis Forga Llenas; Erkuden Aranburu Urtasun; Francisco Sala Pericas; Ramón Angós Musgo; Maria Rosario Mercado Gutierrez; Mercedes Palacios Sarrasqueta Journal: Ann Gastroenterol Date: 2016-12-16
Authors: Susana Hernández-Doño; Roberto Alejandro Sánchez-González; Ma Guadalupe Trujillo-Vizuet; Fabiola Yeseline Zamudio-Castellanos; Rafael García-Silva; Pedro Bulos-Rodríguez; Carlos A Vazquez-Guzmán; Ximena Cárdenas-Ramos; Diana de León Rodríguez; Fabiola Elías; Sergio Domínguez-Arrevillaga; José Manuel Pérez-Tirado; Olga Lidia Vera-Lastra; Julio Granados; Jesús Sepúlveda-Delgado Journal: Clin Immunol Date: 2022-04-05 Impact factor: 10.190